P01.04.A Lesion-symptom mapping based on stroke or glioma: etiology matters!
Authors: E E van Grinsven, A R Smits, E van Kessel, M Raemaekers, E H F de Haan, I M C Huenges-Wajer, V J Ruijters, M E P Philippens, J J C Verhoeff, N F Ramsey, P A J T Robe, T J Snijders, M J E van Zandvoort
Journal: Neuro-Oncology (2022)

Abstract Background Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary as a result of how they affect brain tissue, and how they are distributed. The inclusion of different etiologies would increase the statistical power and improve generalizability of results, but has been critically debated. Findings from lesion studies are a resource for clinicians and used across different etiologies. This study directly compared lesion-symptom maps (LSM) between two populations (diffuse glioma versus ischemic stroke) in order to investigate if brain areas with adequate coverage in both groups, show topographical overlap in lesion-symptom associations. Material and Methods Data from two studies were combined. Both the glioma (N = 196, WHO grade 2-4) and stroke (N = 147) population underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For the purpose of this study, we selected two widely used cognitive tasks, the Rey Auditory Verbal Learning Test and the verbal fluency test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce LSM for these cognitive tasks for both populations separately. Results For both tumor and stroke, our etiology-specific LSM largely followed the expected neuroanatomical pattern based on previous literature. Nevertheless, for both tasks substantial differences in LSM-results were present between the populations in brain areas with adequate coverage in both groups, though we did find similar white matter tracts involved in memory and semantic fluency performance across etiologies. Post-hoc analyses of these locations confirmed an interaction between lesion presence and etiology for a majority of these regions; damage by a tumor, but not a stroke, was related to worse cognitive performance for these regions. Conclusion This study provides the first direct comparison of LSM in a large cohort of patients. Differences in LSM were found between the glioma and stroke group, confirming that etiology matters when investigating the cognitive consequence of lesions. These differences could partly be explained by differences in lesion volume and topography. Nonetheless, the pattern shown by glioma patients on the group level is consistent with localizations found in earlier studies on both stroke and glioma patients using different techniques. While glioma series thus can be used to provide converging evidence about functional localization, we do suggest that findings from LSM studies in neuro-oncological populations should be considered as cause-specific. Findings from functional localization research from non-glioma populations should only be applied to a glioma population with caution.